Fungicidal compositions and their use

ABSTRACT

FUNGICIDAL COMPOSITIONS THAT ARE SUITABLE FOR USE ON LIVING PLANT MATERIALS CONTAIN AS THEIR FUNGICIDALLY-ACTIVE COMPONENT A COMPOUND HAVING THE STRUCTURAL FORMULA   2-(R&#39;&#39;-N(-R)-),1,3-DI(O=),(X)N-ISOINDOLINE   WHEREIN X REPRESENTS A LOWER ALKYL GROUP OR PHENYL; N REPRESENTS AN INTEGER IN THE RAGNE OF 1 TO 4; R REPRESENTS HYDROGEN OR A LOWER ALKYL GROUP; R&#39;&#39; REPRESENTS HYDROGEN, A LOWER ALKYL GROUP, OR THE GROUP -COOR&#34;; AND R&#34; REPRESENTS A LOWER ALKYL GROUP.

United States Patent Oflice 3,798,327 Patented Mar. 19, 1974 US. Cl. 424-274 10 Claims ABSTRACT OF THE DISCLOSURE Fungicidal compositions that are suitable for use on living plant materials contain as their fungicidally-active component a compound havng the structural formula wherein X represents a lower alkyl group or phenyl; n represents an integer in the range of l to 4; R represents hydogen or a lower alkyl group; R represents hydrogen, a lower alkyl group, or the group -COOR"; and R represents a lower alkyl group.

This is a division of my copending application Ser. No. 113,710, now Pat. No. 3,734,925, which was filed on Feb. 8, 197 1.

This invention relates to fungicidal compounds and to a method of controlling the growth of fungi. More particularly, it relates to fungicidal compositions that are suitable for use on living plant materials and to a method of controlling the growth of fungi on the plant materials through the use of these compositions.

In accordance with this invention, it has been found that certain substituted hydrazine compounds are highly effective against a wide variety of plant pathogens, including those responsible for early blight and late blight of tomatoes, cucumber anthracnose, and other serious crop diseases. Because they provide long-lasting protection, fewer applications of these fungicides are required to control plant diseases than are necessary when the previously-"known agricultural fungicides are used.

The substituted hydrazine compounds that are used as the primary fungicidally-active components of the compositions of this invention may be represented by the structural formula wherein X represents an alkyl group having from 1 to 4 carbon atoms or phenyl; n represents an integer in the range of l to 4; R represents hydrogen or an alkyl group having from 1 to 4 carbon atoms; R represents hydrogen, an alkyl group having from 1 to 4 carbon atoms, or the group COOR"; and R" represents an alkyl group having from 1 to 4 carbon atoms. Illustrative of these compounds are 4-butylphthalic hydrazide, 3,4-dipropylphthalic hydrazide, N-(dimethylamino)-2,6-diethylphthalimide, N (isopropylamino)-3,4,5,6-tetraphenylphthal- 7 imide, N (carbpropoxyamino)-2,4-dibutylphthalimide, and the like. A group of the substituted phthalic hydrazides that have been found to be particularly effectlve as fungicides for use on living plants may be represented by the structural formula Ha f I 0 CH1 R (in, g

wherein R, R, and R" have the aforementioned significance. Among the most effective of these compounds as fungicides are the following: N-(carbmethoxyamino)- 3,4-dimethyl 6 isobutylphthalimide, N-(carbbutoxyamino)-3,4-dimethyl-6-isobutylphthalimide, 3,4-dimethyl- 6-isobutylphthalic hydrazide, N-(dimethylamino)-3,4-dimethyl-6-isobutylphthalimide, and N-(dibuty1amino)-3,4- dimethyl-fi-isobutylphthalirnide. One or more of the substituted hydrazides may be present in the fungicidal compositions of this invention.

The fungicidal compounds of this invention may be prepared by any suitable and convenient procedure. For example, they may be prepared by the reaction of a substituted phthalic anhydride with the appropriate hydrazine derivative, such as an alkyl carbazate, an alkyl hydrazine, or hydrazine hydrate. Suitable substituted phthalic anhydrides may be obtained, for example, by the aromatization of products of the condensation of maleic anhydride with dienes, such as 1,3-hexadiene, 2,4-hexadiene, 3- methyl-2,4-hexadiene, 2,4-dimethyl-1,3-pentadiene dimethylbutadienes isoprene, 1,1,3 trimethylbutadiene, 1,1,4 trimethylbutadiene, 1 phenyl-4-methylbutadiene, allo-ocimene, 5-methyl-4-isopropyl-1,3-hexadiene, and the like, by treatment first with palladium and then with an alkaline or acidic aqueous solution.

While the fungicidal compounds of this invention may be applied as such to the soil, they are ordinarily and preferably combined with an inert fungicidal adjuvant carrier and applied as a solution, emulsion, suspension, or dust. Aqueous emulsions or suspensions that contain 4 about 0.001 percent to 1 percent by weight, and preferably 0.01 percent to 0.5 percent by weight, of the active agent are particularly suitable for this use. These compositions may also contain about 0.01 percent to 0.1 percent by weight of a wetting agent, such as an alkyl sul- 50 fate, an alkyl aryl sulfonate, a sulfosuccinate, a polyethylene glycol ether, and the like. Alternatively, the fungicidal compounds may be dissolved in an organic solvent, such as acetone, naphtha, ethylene chloride, or kerosene, and applied as solutions, or they may be mixed 55 with or deposited upon such finely-divided solid carriers as clay, chalk, bentonite, talc, kaolin, fullers earth, and the like and applied as dusts. The fungicidal solutions and dusts preferably contain 1 percent to 50 percent by weight of the fungicidal compound.

The fungicidal compounds may be applied by known techniques to plants, to plant seeds, or to the soil in which plants are growing or are to be grown. For example, they may be applied to the parts of the plants above or in the soil, or the plant seeds may be contacted with the fungicidal compound. Alternatively, the fungicide may be introduced into the soil near the roots of the plants or applied to the surface of the soil and then mixed into the soil to the desired depth.

The amount of the fungicidal composition that is ap- 0 plied is dependent upon such factors as the species of plant being treated and the plant pathogen whose control is desired and is that amount which will inhibit or prevent the growth of the plant pathogen while causing little or no injury to the plants. About 1 pound to 200 pounds of the active compound is ordinarily applied per acre, with particularly good results being obtained when pounds to 35 pounds per acre is used.

The substituted hydrazine compounds may be used as the sole active component of the fungicidal compositions. If desired, however, these compositions may also contain other fungicides, such as sulfur and the metal dimethyldithiocarbamates; insecticides, such as chlordane and benzene hexachloride; or plant nutrients, such as urea, ammonium nitrate, and potash.

The invention is further illustrated by the examples that follows:

EXAMPLE 1 (A) To 476 grams (3.5 moles) of freshly-distilled alloocimene was added a solution of 245 grams (2.5 moles) of maleic anhydride in 720 grams (8.17 moles) of ethyl acetate at such a rate that the temperature rose to 88- 90 C. and remained at that temperature throughout the addition. The reaction mixture was heated With stirring at 88-90 C. for 5 hours and then heated under vacuum to remove the ethyl acetate. The residue was distilled under reduced pressure to remove unreacted alloocimene from the product. There was obtained about 450 grams of 3,4-dimethyl-6-isobutenyltetrahydrophthalic anhydride.

(B) A mixture of 330 grams (1.42 moles) of 3,4-dimethyl-6-isobutenyltetrahydrophthalic anhydride and 20 grams of 5% palladium on carbon was stirred for 6 hours at 260280 C. and then cooled to room temperature. After it had been allowed to stand overnight, the reaction mixture was treated with 820 ml. of a aqueous sodium hydroxide solution, heated at 90-100 C. for 1 hour, diluted with 1700 ml. of Water, and filtered. The filtrate was acidified to pH 5 with hydrochloric acid. The crude product that precipitated was collected. A 90 percent yield of crude 3,4-dimethyl-G-isobutylphthalic anhydride was obtained. This product was used without purification in the preparation of the substituted hydrazine compounds.

(C) A mixture of 23.2 grams (0.1 mole) of 3,4-dimethyl-6-isobutylphthalic anhydride, 10.4 grams (0.1 mole) of ethyl carbazate, and 150 ml. of toluene was heated at its reflux temperature until 1.8 ml. of water had been evolved. After being heated at its reflux temperature for an additional 30 minutes, the reaction mixture was heated at 60 C. under reduced pressure to remove the toluene. There was obtained 30.8 grams of N- (carbethoxyamino)-3,4-dimethyl 6 isobutylphthalimide, which contained 64.0% C, 6.9% H, and 8.8% N (Calculated, 64.2% C, 6.9% H, and 8.8% N). The structure of the compound was confirmed by infrared analysis.

EXAMPLE 2 A mixture of 46.5 grams (0.2 mole) of 3,4-dimethyl- 6-isobutylphthalic anhydride (prepared by the process described in Example 1A and B), 35.3 grams (0.6 mole) of hydrazine hydrate (85 percent in water), and 195 ml. of water was heated at its reflux temperature for 3 hours. The reaction mixture was cooled to room temperature and filtered. The product obtained was washed with water, air dried, and then dried at 60 C. under reduced pressure. There was obtained 48.5 grams of 3,4-dimethyl-6-isobutylphthalic hydrazide that melted at 109-111 C. and contained 68.26% C, 7.40% H, and 11.44% N (calculated, 68.2% C, 7.3% H, and 11.4% N).

EXAMPLE 3 Using the procedure described in Example 1C, tert. butyl carbazate was reacted with 3,4-dimethyl-6-isobutylphthalic anhydride to form N-(carb-tert. butoxyamino)- 3,4-dimethyl-6-isobutylphthalimide in a substantially quantitative yield. The product was a viscous oil that contained 66.7% C, 8.57% H, and 7.78% N (calculated,

4 v 66.0% C, 7.58% H, and 8.1% N). Its structure was confirmed by infrared analysis.

EXAMPLE 4 Using the procedure described in Example 10, asym. dimethylhydrazine was reacted with 3,4-dimethyl-6-isobutylphthalic anhydride to form N-(dimethylamino)-3,4- dimethyl-6-isobutylphthalimide in a yield of 97.5 percent. The product was a waxy solid that contained 70.4% C and 8.7% H (calculated, 70.2% C and 8.1% H). Its structure was confirmed by infrared analysis.

EXAMPLE 5 Aqueous solutions were prepared by dissolving 100 mg. portions of the products of Examples 1-4 in 10 ml. of acetone that contained 2000 p.p.m. of sorbitan trioleate (Span and 5000 ppm. of a polyoxyethylene ether of sorbitan monooleate (Tween The acetone solutions were dispersed in 90 ml. portions of distilled water to form aqueous solutions that contained 1000 p.p.m. of the fungicidal compound. More dilute solutions were prepared by adding distilled water to these solutions.

EXAMPLE 6 A series of experiments was carried out in which tomato plants that had been sprayed with the aqueous solutions of Example 5 were sprayed with a suspension of spores of Alternaria solani, the fungus responsible for early blight of tomatoes. One week after treatment, the degree of suppression of the disease was noted. The results are given in Table I. In no case was there any visible injury to the tomato plant.

l Manganous ethylene bis dithiocarbamate.

EXAMPLE 7 A series of experiments was carried out in which tomato plants that had been sprayed with the aqueous solutions of Example 5 were sprayed with a suspension of spores of Phytophthora infestans, the fungus that causes late blight of tomatoes. One week after treatment, the degree of suppression of the disease was noted. The results are given in Table II. In no case was there visible injury to the tomato plants.

TABLE II Concentration of Percent fungicide in control of aqueous solution late blight Fungicide (p.p.m.) of tomatoes Product of- Example 1 100 98 20 17 4 53 Example 2 250 80 Example 3 100 30 80 Commercial tungicide-Maneb 100 20 97 4 31 None 0 EXAMPLE 8 Tender green bean plants with fully expanded primary leaves were inoculated with spores of Erypsiphe polygoni, the powdery mildew fungus. Forty-eight hours later, the

plants were sprayed with aqueous solutions prepared by 6. A composition for controlling the growth of fungi the process of Example 5. After a period of 7-10 days, on living plants that comprises (a) a fungicidally effective the degree of suppression of the disease was noted. The amount of a substituted hydrazine compound having the results obtained are summarized in Table HI. structural formula TABLE III 5 0 Concentration of aqueous Control or R 1 l a mild Funglclde l ea s 6' N N R' Product 0t 10 Example 1... 1, 000 Good control. Example 2.. 1,000 Do. CH, (H) Example 3 1, (11% Exctillent control. I

0- 20 Good control. Example 4 1, 000 D0.

15 wherein R represents hydrogen or an alkyl group having I claim from 1 to 4 carbon atoms; R represents hydrogen, an alkyl group having from 1 to 4 carbon atoms or the group 1. The method of rotectin hvm lants from attack n, n by fungi which compgses applgying 5 fi Plants a fimgi -COO and R represents an alkyl group having 1 to 4 carbon atoms, and (b) an mert fungicidal ad uVant carcidal amount of a compound having the structural formula Tier therefor 0 0 7. A composition as set forth in claim 6 wherein the a substituted hydrazine compound is N-(carbethoxyamino)- on. 3,4'dimethyl-6-isobutylphthalimide.

NNR' 8. A composition as set forth in claim 6 wherein the substituted hydrazine compound is N-(carb-tert. butoxy- A: C amino)-3,4-dimethyl-6-isobutylphthalimide.

Hi 8 9. A composition as set forth in claim 6 wherein the CH L substituted hydrazine compound is 3,4-dimethyl-6-isobutylphthalic hydrazide.

wherein R represents hydrogen or an alkyl group having 10. A composition as set forth in claim 6 wherein the from 1 to 4 carbon atoms; R represents hydrogen, an substituted hydrazine compound is N-(dimethylamino)- alkyl group having from 1 to 4 carbon atoms, or the group 3,4-dimethyl-6-isobutylphthalimide.

-COOR"; and R" represents an alkyl group having from References Cited 1 to 4 carbon atoms.

2. The method of claim 1 wherein the fungicidal com- UNITED STATES PATENTS pound is N-(carbethoxyamino)-3,4-dimethyl-6-isobutylphthalimide' 2,657,169 10/ 1953 Ligett et a1 424-274 3. The method of claim 1 wherein the fungicidal com- OTHER REFERENCES pound is N- carb-tert. butoxyamino)-3,4-dimethyl-6-isobu- 40 J. Chem. Soc" 1937: 26 33 Drew et aL tYlPhthalmude- J. Prakt. Chem. 30, 204-17 (1965), Heidenbluth et al.

4. The method of claim 1 wherein the fungicidal com- J Chem Soc 1937: 18416 Drew et 31 pound is 3,4dimethyl-6-isobutylphthalic hydrazide.

5. The method of claim 1 wherein the fungicidal comv MEY E pound is N-(dimethylamino) 3,4 dimethyl-6-isobuty1- ALBERT ERsflprmary i h h li jd D. W. ROBINSON, Assistant Examiner 

